Antigenic constituents of human milk or of alternative feedings for infants may be responsible for adverse reactions in a subset of infants with milk protein intolerance. These reactions include those commonly associated with atopy, such as angioedema, urticaria, wheezing, vomiting, and eczema. Pulmonary hemosiderosis, malabsorption with villous atrophy, and eosinophilic enterocolitis, perhaps mediated by immune complexes or T cells, have also been associated with the ingestion of cow's milk proteins and/or soy proteins in infant feedings. Colic, sleeplessness, and irritability are symptoms seen in almost all infants at some time during infancy, including those few infants with immune-mediated reactions to dietary antigens. Determining that adverse reactions are, in fact, immune mediated is often difficult and is accomplished by an in vivo challenge with the potential offending antigen, together with in vitro confirmation of immunoreactivity to the challenge antigen. Double-blind challenge with purified dietary antigens is useful in relating symptoms to a specific antigen, but the results may be difficult to interpret if the appearance of symptoms is delayed beyond several hours in a young infant. In vitro testing is compromised by the presence of some form of immunoreactivity, such as hemagglutinating antibodies, to dietary antigens in a large percentage of infants without symptoms and by lack of standardization of clinical tests for cell-mediated reactions to dietary antigens. Much effort also has been devoted to predicting in which infants immune-mediated reactions to dietary proteins will develop in advance of their introduction into the diet. Increased cord blood IgE concentrations and parental history of atopy place an infant at highest risk for atopic disease during infancy and early childhood.